Prolonged Adjuvant Imatinib Therapy Tied to Extended OS in High-Risk GIST

Prolonged adjuvant imatinib for high-risk gastrointestinal stromal tumors (GIST) patients demonstrated a superior overall survival (OS) over shorter-term imatinib treatment, according to a phase 3 clinical trial comparing 1 year to 3-year imatinib therapy (JAMA Oncol. 2020;6[8]:1241-1246).

Conducted by Heikki Joensuu, MD, Department of Oncology, Helsinki University Hospital, Finland, and his team, the purpose of this trial was to assess the effect adjuvant imatinib had on the OS of patients at a high-risk for GIST recurrence after macroscopically complete surgery.

“Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor, but its influence on overall survival has remained uncertain,” explained Dr Joensuu and colleagues. 

The open-label trial was conducted across Finland, Germany, Norway, and Sweden. It included 400 patients who had undergone macroscopically complete surgery for GIST and had a high estimated risk for recurrence according to the modified National Institutes of Health Consensus Criteria. Patients were enrolled between February 2004 and September 2009, follow-up data were analyzed from September to November 2019.

Patients received imatinib 400 mg daily orally for 12 or 36 months post-surgery. The primary end point was RFS, while secondary objectives included OS and treatment safety.

The intention-to-treat cohort consisted of 397 patients (12-month group, 199; 36-month group, 198), had recorded 94 RFS events and 96 OS events at the median follow-up time of 119 months after the date of randomization. The 5-year RFS in the 36-month group was 71.4%, while the 10-year RFS was 52.5%. Meanwhile, in the 12-month group the 5- and 10-year RFS was 85.5% and 65.3%, respectively (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87; P = .003).

Furthermore, the 5-year and 10-year OS rates in the 36-month group were 92.0% and 79.0%, respectively. The 12-month group saw a 5 and 10-year OS of 85.5% and 65.3% (HR, 0.55; 95% CI, 0.37-0.83; P = .004). 

Results were similar in the efficacy population, which consisted of 15 patients who did not have GIST in the central pathology review and 24 who had intra-abdominal metastases removed (36-month group: 10-year OS, 81.6%; 12-month group: 66.8%; HR, 0.50; 95% CI, 0.32-0.80; P = .003). Researchers did not detect any new safety signals.

“Three years of adjuvant imatinib is superior in efficacy compared with 1 year of imatinib. Approximately 50% of deaths may be avoided during the first 10 years of follow-up after surgery with longer adjuvant imatinib treatment,” concluded Dr Joensuu et al.—Alexandra Graziano